DESCRIPTION: The primary goal of this research is to examine the regulation of LHRH neuronal activation associated with the ovulatory LH surge. Proposed experiments will continue to use expression of the immediate early gene product, cFos, as a marker of stimulated neuronal activity within LHRH neurons and their afferents, in conjunction with tract-tracing and in situ hybridization, to further explore neuronal mechanisms triggering the preovulatory LH surge. In addition, this proposal will focus on the role of estrogens (i.e., their positive feedback effects) in altering neuronal function in preparation for LHRH neuronal activation associated with the ovulatory LH surge. Moreover, increased galanin expression in LHRH neurons and increased LHRH transcription observed during the period of post-trigger enhancement when cFos is expressed in LHRH neurons prompt investigation into the cellular consequences of LHRH neuronal activation. Specifically these studies will: AIM 1) Characterize the role of periventricular preoptic area neurons on LHRH activation during spontaneous and steroid-induced LH surges by addressing the following questions: Does elimination of periventricular preoptic area neurons alter LHRH activation? Do periventricular preoptic area tyrosine hydroxylase-positive neurons make dopamine? Do LHRH neurons have dopamine or alpha-noradrenergic receptors; does dopamine acting on alpha receptors mediate LHRH stimulation? Are the periventricular preoptic area tyrosine hydroxylase-positive neurons the same neurons that express neurotensin and stimulate LHRH function? Are GABA neurons in the preoptic area stimulated at the time of an LH surge? AIM 2) Characterize the activation of preoptic area/hypothalamic neurons during the period for estrogen's positive feedback effects by addressing the following questions: Does estrogen's positive feedback effects alter tyrosine hydroxylase and neurotensin gene expression in the periventricular preoptic area neurons; what is the time course for estrogen's effects? Which neurons are activated during the period for effective estrogen positive feedback prior to the onset of the LH surge? What are the efferent projections from the identified neurons, i.e., their relationship to periventricular preoptic and LHRH neurons? AIM 3) Determine the role cFos has in the increased gene expression of galanin and LHRH associated with LHRH neuronal activation by addressing the following questions: Are changes in galanin and LHRH mRNA expression in LHRH neurons more closely linked to expression of cFos in LHRH neurons or to LHRH release? Can blockade of cFos expression in LHRH neurons block the induction of galanin, decrease LHRH mRNA in LHRH neurons and alter the LH surge or LHRH release? These studies will generate new information about the reproductive neuroendocrine axis, particularly the neuronal mechanisms involved in activating LHRH neurons during this most critical event.